Cervical precancer and cancer risk by human papillomavirus status and cytologic interpretation: Implications for risk-based management

Philip E. Castle, Shagufta Aslam, Catherine Behrens

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: Cervical cancer risks, estimated by using cervical intraepithelial neoplasia grade 3 (CIN3) or more severe diagnoses (>CIN3) endpoints, have not been quantified for different combinations of results from currently approved screening methods. Understanding these risks will guide optimal patient management. Methods:Women aged >25 years (n= 7,823) underwent highrisk human papillomavirus (hrHPV) and liquid-based cytology (LBC) testing. Women with hrHPV-positive results and/or abnormal LBC, plus a random subset of hrHPV and LBC negatives, underwent colposcopy; those without >CIN2 at baseline were screened annually by LBC and referred to colposcopy for an abnormal LBC (n = 7,392). One- and 3-year >CIN3 risks with 95% confidence intervals (95% CI) were calculated for paired hrHPV and LBC (hrHPV/LBC) results. Results: One-year >CIN3 risks ranged from 81.27% (95% CI, 66.02%-90.65%) for HPV16 positive/high-grade to 0.33% (95% CI, 0.18%-0.62%) for hrHPV negative/negative for intraepithelial lesion or malignancy (NILM). One-year >CIN3 risk for HPV16/NILM (13.95%; 95% CI, 10.98%-17.58%) was greater than low-grade squamous intraepithelial lesion (LSIL; 7.90%; 95% CI, 5.99%-10.37%; P = 0.002) and similar to hrHPVpositive/ LSIL (11.45%; 95% CI, 8.61%-15.07%; P = 0.3). Three-year >CIN3 risks for HPV16 positive/LSIL and HPV16/ atypical squamous cells of undetermined significance was 24.79% (95% CI, 16.44%-35.58%) and 24.36% (95% CI, 15.86%-35.50%), respectively, and 0.72% (95% CI, 0.45%-1.14%) for hrHPV negative/NILM. Conclusions: hrHPV and LBC results stratify cervical cancer risk by more than two orders of magnitude. HPV16-positive women, regardless of the LBC result, warrant immediate colposcopy. Women with concurrent HPV16 and high-grade LBC might consider treatment without a confirmatory biopsy with informed decision-making with their provider. Impact: These results provide relevant benchmarks for riskbased cervical cancer screening and management.

Original languageEnglish (US)
Pages (from-to)1595-1599
Number of pages5
JournalCancer Epidemiology Biomarkers and Prevention
Volume25
Issue number12
DOIs
StatePublished - Dec 1 2016

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Risk Management
Uterine Cervical Neoplasms
Cell Biology
Cervical Intraepithelial Neoplasia
Confidence Intervals
Colposcopy
Benchmarking
Neoplasms
Early Detection of Cancer
Decision Making
Biopsy

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Cervical precancer and cancer risk by human papillomavirus status and cytologic interpretation : Implications for risk-based management. / Castle, Philip E.; Aslam, Shagufta; Behrens, Catherine.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 25, No. 12, 01.12.2016, p. 1595-1599.

Research output: Contribution to journalArticle

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title = "Cervical precancer and cancer risk by human papillomavirus status and cytologic interpretation: Implications for risk-based management",
abstract = "Background: Cervical cancer risks, estimated by using cervical intraepithelial neoplasia grade 3 (CIN3) or more severe diagnoses (>CIN3) endpoints, have not been quantified for different combinations of results from currently approved screening methods. Understanding these risks will guide optimal patient management. Methods:Women aged >25 years (n= 7,823) underwent highrisk human papillomavirus (hrHPV) and liquid-based cytology (LBC) testing. Women with hrHPV-positive results and/or abnormal LBC, plus a random subset of hrHPV and LBC negatives, underwent colposcopy; those without >CIN2 at baseline were screened annually by LBC and referred to colposcopy for an abnormal LBC (n = 7,392). One- and 3-year >CIN3 risks with 95{\%} confidence intervals (95{\%} CI) were calculated for paired hrHPV and LBC (hrHPV/LBC) results. Results: One-year >CIN3 risks ranged from 81.27{\%} (95{\%} CI, 66.02{\%}-90.65{\%}) for HPV16 positive/high-grade to 0.33{\%} (95{\%} CI, 0.18{\%}-0.62{\%}) for hrHPV negative/negative for intraepithelial lesion or malignancy (NILM). One-year >CIN3 risk for HPV16/NILM (13.95{\%}; 95{\%} CI, 10.98{\%}-17.58{\%}) was greater than low-grade squamous intraepithelial lesion (LSIL; 7.90{\%}; 95{\%} CI, 5.99{\%}-10.37{\%}; P = 0.002) and similar to hrHPVpositive/ LSIL (11.45{\%}; 95{\%} CI, 8.61{\%}-15.07{\%}; P = 0.3). Three-year >CIN3 risks for HPV16 positive/LSIL and HPV16/ atypical squamous cells of undetermined significance was 24.79{\%} (95{\%} CI, 16.44{\%}-35.58{\%}) and 24.36{\%} (95{\%} CI, 15.86{\%}-35.50{\%}), respectively, and 0.72{\%} (95{\%} CI, 0.45{\%}-1.14{\%}) for hrHPV negative/NILM. Conclusions: hrHPV and LBC results stratify cervical cancer risk by more than two orders of magnitude. HPV16-positive women, regardless of the LBC result, warrant immediate colposcopy. Women with concurrent HPV16 and high-grade LBC might consider treatment without a confirmatory biopsy with informed decision-making with their provider. Impact: These results provide relevant benchmarks for riskbased cervical cancer screening and management.",
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N2 - Background: Cervical cancer risks, estimated by using cervical intraepithelial neoplasia grade 3 (CIN3) or more severe diagnoses (>CIN3) endpoints, have not been quantified for different combinations of results from currently approved screening methods. Understanding these risks will guide optimal patient management. Methods:Women aged >25 years (n= 7,823) underwent highrisk human papillomavirus (hrHPV) and liquid-based cytology (LBC) testing. Women with hrHPV-positive results and/or abnormal LBC, plus a random subset of hrHPV and LBC negatives, underwent colposcopy; those without >CIN2 at baseline were screened annually by LBC and referred to colposcopy for an abnormal LBC (n = 7,392). One- and 3-year >CIN3 risks with 95% confidence intervals (95% CI) were calculated for paired hrHPV and LBC (hrHPV/LBC) results. Results: One-year >CIN3 risks ranged from 81.27% (95% CI, 66.02%-90.65%) for HPV16 positive/high-grade to 0.33% (95% CI, 0.18%-0.62%) for hrHPV negative/negative for intraepithelial lesion or malignancy (NILM). One-year >CIN3 risk for HPV16/NILM (13.95%; 95% CI, 10.98%-17.58%) was greater than low-grade squamous intraepithelial lesion (LSIL; 7.90%; 95% CI, 5.99%-10.37%; P = 0.002) and similar to hrHPVpositive/ LSIL (11.45%; 95% CI, 8.61%-15.07%; P = 0.3). Three-year >CIN3 risks for HPV16 positive/LSIL and HPV16/ atypical squamous cells of undetermined significance was 24.79% (95% CI, 16.44%-35.58%) and 24.36% (95% CI, 15.86%-35.50%), respectively, and 0.72% (95% CI, 0.45%-1.14%) for hrHPV negative/NILM. Conclusions: hrHPV and LBC results stratify cervical cancer risk by more than two orders of magnitude. HPV16-positive women, regardless of the LBC result, warrant immediate colposcopy. Women with concurrent HPV16 and high-grade LBC might consider treatment without a confirmatory biopsy with informed decision-making with their provider. Impact: These results provide relevant benchmarks for riskbased cervical cancer screening and management.

AB - Background: Cervical cancer risks, estimated by using cervical intraepithelial neoplasia grade 3 (CIN3) or more severe diagnoses (>CIN3) endpoints, have not been quantified for different combinations of results from currently approved screening methods. Understanding these risks will guide optimal patient management. Methods:Women aged >25 years (n= 7,823) underwent highrisk human papillomavirus (hrHPV) and liquid-based cytology (LBC) testing. Women with hrHPV-positive results and/or abnormal LBC, plus a random subset of hrHPV and LBC negatives, underwent colposcopy; those without >CIN2 at baseline were screened annually by LBC and referred to colposcopy for an abnormal LBC (n = 7,392). One- and 3-year >CIN3 risks with 95% confidence intervals (95% CI) were calculated for paired hrHPV and LBC (hrHPV/LBC) results. Results: One-year >CIN3 risks ranged from 81.27% (95% CI, 66.02%-90.65%) for HPV16 positive/high-grade to 0.33% (95% CI, 0.18%-0.62%) for hrHPV negative/negative for intraepithelial lesion or malignancy (NILM). One-year >CIN3 risk for HPV16/NILM (13.95%; 95% CI, 10.98%-17.58%) was greater than low-grade squamous intraepithelial lesion (LSIL; 7.90%; 95% CI, 5.99%-10.37%; P = 0.002) and similar to hrHPVpositive/ LSIL (11.45%; 95% CI, 8.61%-15.07%; P = 0.3). Three-year >CIN3 risks for HPV16 positive/LSIL and HPV16/ atypical squamous cells of undetermined significance was 24.79% (95% CI, 16.44%-35.58%) and 24.36% (95% CI, 15.86%-35.50%), respectively, and 0.72% (95% CI, 0.45%-1.14%) for hrHPV negative/NILM. Conclusions: hrHPV and LBC results stratify cervical cancer risk by more than two orders of magnitude. HPV16-positive women, regardless of the LBC result, warrant immediate colposcopy. Women with concurrent HPV16 and high-grade LBC might consider treatment without a confirmatory biopsy with informed decision-making with their provider. Impact: These results provide relevant benchmarks for riskbased cervical cancer screening and management.

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